Initial Specimen Diversion Device® reduces blood culture contamination and vancomycin use in academic medical centre.

BACKGROUND: In suspected bloodstream infections, accurate blood culture results are critical to timely diagnoses and appropriate antibiotic administration. AIM: An Initial Specimen Diversion Device®, Steripath® (Magnolia Medical Technologies, Seattle, WA, USA) was evaluated for efficacy in reducing blood culture contamination at Brooke Army Medical Center (6.8% six-month contamination rate prior to intervention) in a six-month quality improvement project. METHODS: Blood cultures in the emergency department were collected using either Steripath or the standard method. Blood samples of 20 mL were cultured into an aerobic and anaerobic medium and incubated for five days using an automated microbial detection system immediately after collection. Positive bottles were Gram-stained and plated. Rapid molecular polymerase chain reaction identification was performed on all first positive bottles within a blood culture set for each admission or ED visit. Speciation was deduced during antimicrobial sensitivity testing using the Vitek-2 instrument. FINDINGS: Seven out of 1016 (0.69%) contamination events occurred when using Steripath vs 53 out of 800 (6.6%) contamination events when using the standard method. Steripath use was associated with a 90% lower incidence of blood culture contamination vs the standard method. Post study, Steripath use was implemented as standard practice hospital-wide, and a retrospective data analysis attributed a 31.4% decrease in vancomycin days of therapy to Steripath adoption. CONCLUSION: Using Steripath significantly decreased blood culture contamination events for bacterial bloodstream infections compared to the standard method. Subsequent adoption of Steripath reduced overall vancomycin usage. With widescale implementation Steripath could bolster antibiotic stewardship, mitigating antibiotic resistance caused by unnecessary antibacterial treatments.

Characterizing atomic magnetic gradiometers for fetal magnetocardiography.

Atomic magnetometers (AMs) offer many advantages over superconducting quantum interference devices due to, among other things, having comparable sensitivity while not requiring cryogenics. One of the major limitations of AMs is the challenge of configuring them as gradiometers. We report the development of a spin-exchange relaxation free vector atomic magnetic gradiometer with a sensitivity of 3 fT cm-1 Hz-1/2 and common mode rejection ratio >150 in the band from DC to 100 Hz. We introduce a background suppression figure of merit for characterizing the performance of gradiometers. It allows for optimally setting the measurement baseline and for quickly assessing the advantage, if any, of performing a measurement in a gradiometric mode. As an application, we consider the problem of fetal magnetocardiography (fMCG) detection in the presence of a large background maternal MCG signal.

Parameters for successful monthly extended dosing of darbepoetin-alpha in patients undergoing hemodialysis.

AIM: To document the feasibility and report the results of dosing darbepoetin-alpha at extended intervals up to once monthly (QM) in a large dialysis patient population. MATERIAL: 175 adult patients treated, at 23 Swiss hemodialysis centres, with stable doses of any erythropoiesis-stimulating agent who were switched by their physicians to darbepoetin-alpha treatment at prolonged dosing intervals (every 2 weeks [Q2W] or QM). METHOD: Multicentre, prospective, observational study. Patients' hemoglobin (Hb) levels and other data were recorded 1 month before conversion (baseline) to an extended darbepoetin-alpha dosing interval, at the time of conversion, and once monthly thereafter up to the evaluation point (maximum of 12 months or until loss to follow-up). RESULTS: Data for 161 evaluable patients from 23 sites were included in the final analysis. At 1 month prior to conversion, 73% of these patients were receiving darbepoetin-alpha weekly (QW) and 27% of the patients biweekly (Q2W). After a mean follow-up of 9.5 months, 34% received a monthly (QM) dosing regimen, 52% of the patients were receiving darbepoetin-alpha Q2W, and 14% QW. The mean (SD) Hb concentration at baseline was 12.3 +/- 1.2 g/dl, compared to 11.9 +/- 1.2 g/dl at the evaluation point. The corresponding mean weekly darbepoetin-alpha dose was 44.3 +/- 33.4 microg at baseline and 37.7 +/- 30.8 microg at the evaluation point. CONCLUSIONS: Conversion to extended darbepoetin-alpha dosing intervals of up to QM, with maintenance of initial Hb concentrations, was successful for the majority of stable dialysis patients.

Biocompatibility of supercritical CO2-treated titanium implants in a rat model.

Supercritical phase CO2 is a promising method for sterilizing implantable devices and tissue grafts. The goal of this study is to evaluate the biocompatibility of titanium implants sterilized by supercritical phase CO2 in a rat subcutaneous implantation model. At 5 weeks post implantation titanium implants sterilized by supercritical phase CO2 produce a soft tissue reaction that is comparable to other methods of sterilization (steam autoclave, ultraviolet light radiation, ethylene oxide gas, and radio-frequency glow-discharge), as indicated by the thickness and density of the foreign body capsule, although there were some differences on the capillary density. Overall the soft tissue response to the implants was similar among all methods of sterilization, indicating supercritical phase CO2 treatment did not compromise the biocompatibility of the titanium implant.

Evidence for a role for anti-Mullerian hormone in the suppression of follicle activation in mouse ovaries and bovine ovarian cortex grafted beneath the chick chorioallantoic membrane.

The first critical transition in follicular development, the activation of primordial follicles to leave the pool of resting follicles and begin growth, is poorly understood, but it appears that the balance between inhibitory and stimulatory factors is important in regulating the exodus of follicles from the resting pool. There is evidence that anti-Mullerian hormone (AMH; also known as MIS) inhibits follicle activation in mice, but whether it plays a similar role in non rodent species is not known. When pieces of bovine ovarian cortex, rich in primordial follicles, are cultured in serum-free medium, most follicles initiate growth, but when cortical pieces are grafted beneath the chorioallantoic membrane (CAM) of chick embryos, follicle activation does not occur. Since embryonic chick gonads of both sexes produce and secrete high levels of AMH, the hypothesis that the AMH in the chick circulation inhibits follicle activation was tested. In Experiment 1, whole newborn mouse ovaries were grafted beneath the CAM (placed "in ovo") or cultured in vitro for 8 days. In vitro (or after 8 days in vivo) follicles activated and proceeded to the primary or secondary stage, but activation was suppressed in ovo. This inhibition was reversed if ovaries were removed from beneath the CAM and cultured in vitro. In contrast, when ovaries from mice null mutant for the AMH type II receptor were CAM-grafted in Experiment 2, follicle activation occurred in a similar fashion to activation in vitro. This finding strongly implicates AMH as the inhibitor of follicle activation in ovo. Since chick embryonic gonads are the source of circulating AMH, chicks were gonadectomized in Experiment 3, prior to grafting of pieces of bovine ovarian cortex beneath their CAMs. Bovine primordial follicles activated in the gonadectomized chicks, similar to the results for mice lacking the AMH type II receptor. Taken together these experiments provide strong evidence that AMH is the inhibitor of mouse follicle activation present in the circulation of embryonic chicks and provide indirect, and hence more tentative, evidence for AMH as an inhibitor of bovine follicle activation.

[Impaired cerebral autoregulation in asymptomatic patients with carotid artery stenosis: comparison of acetazolamide-SPECT and transcranial CO(2)-dopplersonography]. / Störung der zerebralen Perfusionsreserve.

PURPOSE: The indication for operation in patients with asymptomatic high-grade carotid artery stenosis is still under debate. Since impaired cerebrovascular autoregulation is associated with an increased risk for ischaemic events, assessment of cerebral vascular reactivity might be a valuable selection criterion for surgery. The aim of our study was therefore to evaluate the incidence of impaired autoregulation in asymptomatic patients with acetazolamide-single photon emission computed tomography (ACZ-SPECT) and transcranial CO (2)-dopplersonography (CO (2)-TCD). Furthermore, both methods were compared in regard to results and clinical practicability. METHODS: In 42 patients with high-grade (> 70 %) asymptomatic carotid artery stenosis, cerebral perfusion and vascular reactivity were assessed with resting and ACZ-enhanced SPECT scans. In 31 of these patients the CO (2) reactivity of cerebral perfusion was determined by TCD and expressed as normalized autoregulation reserve (NAR). RESULTS: Cerebral perfusion was decreased in 14.3 %. In ACZ-SPECT 26 % and in CO (2)-TCD 28 % revealed an impaired vascular reactivity. Conformity of both methods was high (kappa = 0.93). TCD was superior in practicability, but only applicable in 81 % due to a missing temporal bone window for insonation. CONCLUSION: In accordance ACZ-SPECT and CO (2)-TCD could detect impaired vascular reactivity in a quarter of asymptomatic patients. Both TCD and SPECT could be of value for preoperative selection in this group of patients, whereby sonography is recommended for daily diagnostic work-up.

Transperitoneal versus retroperitoneal approach for treatment of infrarenal aortic aneurysms: is one superior?

BACKGROUND: As endovascular treatment of asymptomatic infrarenal abdominal aortic aneurysm (AAA) increasingly competes with surgical repair, it is necessary to optimize the surgical technique. The aim of this study was therefore to evaluate the superiority of either retroperitoneal (RP) or transperitoneal (TP) approach. PATIENTS AND METHODS: Intra- and peri-operative data from 80 patients with infrarenal AAA and tube graft repair were analysed retrospectively. The RP-approach was used in 37 patients and in 43 the transperitoneal. RESULTS: There was no relevant difference in demographic data and anaesthetic regime; exceptions were differences between the two groups in terms of age (median RP 72.31 vs. TP 68.58 years, p = 0.0174), hypertension (RP 26/37 vs. TP 40/43, p = 0.0019), smoking (RP 25/37 vs. TP 38/43, p = 0.0462), pulmonary diseases (RP 15/37 vs. TP 7/43, p = 0.0232), and previous abdominal surgery (RP 3/37 vs. TP 12/43, p = 0.042). No patient died during the first 30 post-operative days. The RP-group had a longer cross-clamping time (median RP 50 vs. TP 45 min, p = 0.0115) but no difference was found in operating time. Intra-operative blood loss was higher in the RP-group (median RP 800 vs. TP 500 ml, p = 0.033) with an increased need for blood substitutes (median RP 1 vs. TP 0 packed red cells, p = 0.0068). Time spent in ICU was shorter (median RP 24 vs. TP 46 hours, p = 0.0104), but duration of hospitalisation was longer for the RP-group (median RP 13 vs. TP 10.5 days, p = 0.0156). No differences were found in the need for analgesics, the frequency of procedure related complications, and post-operative recovery. CONCLUSIONS: Surgical repair of AAA in selected patients by tube graft placement is a safe procedure independent of the approach. In particular, our findings do not support previously reported superiority of the RP-approach.

Early carotid endarterectomy in patients with a nondisabling ischemic stroke: results of a retrospective analysis.

BACKGROUND: There are several recent recommendations not to delay carotid endarterectomy (CEA) for at least 4 weeks in patients experiencing a nondisabling ischemic stroke. Therefore, we re-examined if these patients could be safely operated on earlier: The aim of our study was to review the perioperative stroke and death rates of CEA performed within 30 days of stroke onset. PATIENTS AND METHODS: During a 4 year period until December 2001, in 66 neurologically stable patients suffering a nondisabling stroke ipsilateral to a carotid artery stenosis > 50% CEA was performed after a median interval of 10 (1-28) days. The modified Rankin scale (mRS) was applied to characterize the severity of impairment of daily living activities pre- and postoperatively: Any postoperative deterioration > 24 hours on the mRS was considered as a new stroke. RESULTS: Operative mortality was 0%, and postoperative neurologic worsening > 24 hours occurred in 8/66 patients (12.1%). In 5/8 patients neurologic deterioration resolved within 5 days after surgery, only one stroke was permanent (1.5%). There was no correlation between timing of surgery or the presence of acute ipsilateral cranial CT defects with the occurrence of postoperative stroke. Stroke severity grading on admission according to the mRS, however, emerged to be a significant determinant of postoperative outcome: While 6/23 patients (26%) with an initial deficit > or = 3 on the mRS developed neurologic worsening, this was the case in only 2/43 patients (4.6%) with a deficit < or = 2 (Odds Ratio 7.2; 95% CI 1.32-39.49; two-sided p = 0.01). CONCLUSION: Our results suggest that selected patients with a minor stroke (mRS < or = 2 on admission) can safely undergo early CEA.

Bovine ovarian cortical pieces grafted to chick embryonic membranes: a model for studies on the activation of primordial follicles.

BACKGROUND: Little is known about the factors that control the initiation of growth of primordial follicles. Primordial follicles in pieces of fetal bovine ovarian cortex spontaneously activate in vitro and develop to the primary stage, but few follicles develop further. For decades, embryologists have grafted tissue to the chorioallantoic membrane (CAM) of chick embryos to study the development of various organs and structures. METHODS AND RESULTS: To test the hypothesis that grafting cortical pieces beneath the CAM membrane of 6-day-old chick embryos ('in ovo') would support the activation of primordial follicles and the growth of activated follicles to the secondary stage, ovarian cortical pieces from six bovine fetuses (6-8 months gestation) were placed either in ovo or in organ culture in serum-free medium (in vitro). Cortical pieces were retrieved after 0, 2, 4, 7, or 10 days in ovo or in vitro. Histological examination revealed a dramatic infiltration of the CAM-grafted cortical pieces with blood vessels. By day 2 in vitro, the number of primordial follicles had declined by 87% concomitant with a 3.5-fold increase in primary follicles (P < 0.01), providing evidence of the expected activation of primordial follicles. Unexpectedly, primordial follicles were not activated in CAM-grafted tissue, as shown by maintenance of their numbers and lack of increase in primary follicles during 10 days in ovo. In experiment 2, a subset of pieces was switched from culture to CAM grafts and from CAM grafts to culture on day 2. The CAM did not support the growth of primary follicles activated in vitro, apparently because the activated follicles did not survive the transfer (P < 0.05). However, primordial follicles maintained in ovo retained their ability to activate; after their removal from the CAM into culture, primordial follicles decreased in number and primary follicles increased in number within 2 days (P < 0.05). CONCLUSIONS: The CAM graft will provide a useful model for studying the factors involved in activation of primordial follicles.

Survival of Chlamydia pneumoniae-infected Mono Mac 6 cells is dependent on NF-kappaB binding activity.

The respiratory tract pathogen Chlamydia pneumoniae has been associated with atherosclerosis. Monocytes are supposed to serve as a vehicle for systemic dissemination of intracellular C. pneumoniae from the lung to the artery vessel wall. We were therefore interested in pathogen-induced cellular events associated with NF-kappaB, a crucial transcription factor for both inflammatory cytokines and antiapoptotic molecules. In this study we demonstrate by electrophoretic mobility shift assay that C. pneumoniae infection of the human monocytic cell line Mono Mac 6 induces activation of NF-kappaB over 48 h, with a maximum level at 1 h postinfection. As shown by supershift assay, the activated NF-kappaB complex consists of the subunits RelA (p65) and NF-kappaB1 (p50). Apoptotic host cells were not detected during the early stages of the infection when maximal activation of NF-kappaB was detected. Pretreatment of Mono Mac 6 with the antioxidant and NF-kappaB inhibitor PDTC (pyrrolidine dithiocarbamate) induced activation of caspase-3 and led to apoptotic cell death. The C. pneumoniae-induced activation of the NF-kappaB complex was reduced by PDTC, which in parallel resulted in an increased apoptosis, as quantified by annexin V labeling and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling reaction. In the complete absence of activated NF-kappaB, when Mono Mac 6 cells were pretreated with the more potent NF-kappaB inhibitors MG-132 and parthenolide a C. pneumoniae-mediated rescue of cells from induced apoptosis could not be achieved. Our results indicate that activation of NF-kappaB in C. pneumoniae-infected Mono Mac 6 cells is associated with protection of Mono Mac 6 cells against apoptosis and might thereby contribute to systemic spread of the pathogen.

Routine mutation screening of HNF-1alpha and GCK genes in MODY diagnosis: how effective are the techniques of DHPLC and direct sequencing used in combination?

AIMS/HYPOTHESIS: Mutations in the hepatocyte nuclear factor (HNF)-1alpha and glucokinase (GCK) genes are the major causes of monogenic forms of Type II (non-insulin-dependent) diabetes mellitus (Maturity-Onset Diabetes of the Young subtypes, MODY). We evaluated the effectiveness of fluorescent single-strand conformation polymorphism (F-SSCP), denaturing high-performance liquid chromatography (DHPLC) and sequencing based mutation detection in the molecular diagnosis of MODY. Our goal is to identify a rapid, efficient and cost effective mutation detection method for the molecular diagnosis of MODY and other human genetic disorders. METHODS: We evaluated the accuracy of DHPLC in screening for MODY 2 and 3 mutations. In addition, we compared the sensitivity, specificity, cost, handling time and analysis time of fluorescent single-strand conformation polymorphism, denaturing high-performance liquid chromatography and direct sequencing screening methods. RESULTS: Denaturing high-performance liquid chromatography is a recently developed method for mutation detection. It is cost effective, powerful and reliable and quite suitable for 22 out of the 24 fragments required for MODY 2 and 3 testing. However, exons 1 and 7 of the HNF-1alpha gene are very polymorphic and so direct sequencing is faster as well as more efficient and reliable. CONCLUSION/INTERPRETATION: Our results suggest that combining denaturing high-performance liquid chromatography and direct sequencing is a good approach for the routine detection of HNF-1alpha and GCK mutations in MODY families. Denaturing high-performance liquid chromatography appears to be a powerful tool in genetic testing and the method could be applied to the molecular diagnosis of other human genetic diseases.

Cryptic responses to tissue manipulations in avian embryos.

Experimental embryology performed on avian embryos combines tissue manipulations and cell-labeling methods with increasing opportunities and demands for critical assays of the results. These approaches continue to reveal unexpected complexities in the normal patterns of cell movement and tissue origins, documentation of which is critical to unraveling the intricacies of cell and tissue interactions during embryogenesis. Viktor Hamburger's many pioneering contributions helped launch and promote the philosophical as well as technical elements of avian experimental embryology. Furthermore, his scholarship and profoundly positive presence influenced not just those of us fortunate to have trained with him, but several generations of developmental biologists. The first part of this article presents examples of the opportunities and rewards that have occurred due to his influences. Surgical manipulation of avian embryonic tissues always introduces a greater number of variables than the experimenter can control for or, often, readily identify. We present the results of dorsal and ventral lesions of hindbrain segments, which include defects in structures within, beside, and also at a considerable distance from the site of lesion. Extramedullary loops of longitudinal tract axons exit and re-enter the neural tube, and intra-medullary proliferation of blood vessels is expanded. Peripherally, the coalescence of neural crest- and placode-derived neuroblasts is disrupted. As expected, motor neurons and their projections close to the sites of lesion are compromised. However, an unexpected finding is that the normal projections of cranial nerves located distant to the lesion site were also disrupted. Following brainstem lesions in the region of rhombomeres 3, 4 or 5, trigeminal or oculomotor axons penetrated the lateral rectus muscle. Surprisingly, the ability of VIth nerve axons to reach the lateral rectus muscle was not destroyed in most cases, even though the terrain through which they needed to pass was disrupted. These axons typically followed a more ventral course than normal, and usually, the axons emerging from individual roots failed to fasciculate into a common VIth nerve, which suggests that each rootlet contains pathfinder-competent axons. The lesson from these lesions is that surgical intervention in avian embryos may have substantial effects upon tissues within, adjacent to, and distant to those that are being manipulated.

Thermal destruction of benzene.

The thermal destruction of benzene in methane/air flue gas is studied experimentally using an atmospheric laminar flow reactor in laboratory scale. The reactor is operated at four different fuel equivalent ratios (phi = 0.06, 0.1,0.5, 3.7), and temperatures in the range from 850 to 973 K and realises a residence time of 5 s. Stable-species concentrations are measured by gas chromatography (GC) and high-pressure liquid chromatography (HPLC), where phenol, acetylene, formaldehyde, acrolein, methane and acetaldehyde are the major hydrocarbon products besides CO and CO2. The augmentation of the temperature from 850 to 973 K increases the benzene conversion rate from 55% to 99%. The experimental results for one fuel equivalent ratio (phi = 0.5) are compared to the benzene model proposed by Emdee et al. (J. Phys. Chem. 92 (1992) 2151-2161). A fair agreement is observed for the benzene consumption and the CO production throughout the temperature range considered here. The small hydrocarbons are not very well matched, which requires further research on the sub-models. Our experimental results on laboratory scale provide a database for the modelling of benzene oxidation in waste incinerators.

The primordial to primary follicle transition.

The mechanisms that regulate the gradual exit of ovarian follicles from the non-growing, primordial pool are very poorly understood. A better understanding of the signals that initiate follicular growth in mammals, and of the conditions necessary for sustained growth of early preantral follicles in vitro, could have practical implications for contraception, alleviation of infertility, and regulation of the rate of follicle depletion (menopause). Our laboratory has developed two experimental systems that can be used to study factors involved in the activation of primordial follicles. In the first experimental system, small pieces of ovarian cortex, containing mostly primordial follicles, are isolated from fetal ovaries of cattle or baboons and cultured in serum-free medium. Under these conditions most primordial follicles become activated between 12 and 24 h of culture; their granulosa cells change shape, from flattened to cuboidal, and begin to express proliferating cell nuclear antigen (PCNA). During 7 days in culture, the newly-formed primary follicles and their oocytes increase significantly in diameter. This wholesale 'spontaneous' activation in serum-free medium is quite different from the much more gradual exit of primordial follicles from the resting pool that occurs in vivo and suggests that primordial follicles in vivo may be subject to a tonic inhibition of growth initiation or, alternatively, that some aspect(s) of the environment in vitro stimulates growth initiation. Recently we developed a second experimental system for studying activation of primordial follicles. Pieces of ovarian cortex from bovine or baboon fetuses were grafted beneath the developing chorioallantoic membrane (CAM) of 6-day-old chick embryos, a site known to support xenografted tissues. The cortical pieces were rapidly vascularized and histological analysis of pieces recovered after 2, 4, 7, or 10 days 'in ovo' revealed no increase in the number of primary follicles and maintenance of original numbers of primordial follicles. Therefore, grafting ovarian cortical pieces beneath the chick CAM provides an experimental system in which follicles remain at the primordial stage in a readily accessible environment and which, thus, may be used to study potential regulators of the initiation of follicle growth. The results suggest that vascularization of isolated pieces of ovarian cortex provides conditions that maintain follicular quiescence, whereas culture in vitro allows unrestrained activation of primordial follicles. Future studies with and comparisons of the in vitro and in ovo models may provide new insight into the mechanisms that regulate the primordial to primary follicle transition.

[Kidney calculi--is nutrition a trigger or treatment?]. / Nierensteine--ist die Ernährung Trigger oder Therapeutikum?

Kidney stones occur in up to 15% of the population. The incidence of stone disease is 0.1-0.4%, i.e. 100 to 400 out of 100,000 people form a kidney stone every year. The recurrence rate is high, reaching 52% within 10 years and 75% within 20 years, respectively. Since urinary supersaturation, the driving force for crystallisation and stone formation, directly depends on nutritional habits, dietary recommendations are an important part of stone treatment. The benefit of urine dilution by means of a high fluid intake (urine volume at least 2.5 L/d) has been established by several studies. On the other hand, incorrect dietary recommendations, such as the restriction of calcium as advocated for decades, can even promote stone formation! Indeed, large prospective trials have clearly demonstrated that the risk for stone formation decreases with increasing daily calcium intake. It is therefore mandatory that low-calcium diet is finally abandoned in patients with calcium kidney stones and replaced by a sufficient calcium consumption, i.e. 1200 mg per day. Furthermore, epidemiological studies confirm that a diet rich in meat protein carries an increased risk for forming upper urinary tract stones; thus, daily protein intake should not exceed 1 g/kg body weight, which corresponds with general recommendations for a healthy diet. Last but not least, more recent studies have shown that the consumption of high quantities of fruits and vegetables may protect against kidney stone formation, since it raises urinary excretion of citrate, an important inhibitor of crystallization. The present review emphasizes on the relations between nutrition and stone formation in the urinary tract and offers convenient and inexpensive measures for the prevention of recurrence of nephrolithiasis.

Hemoglobin protects from streptococcal cell wall-induced arthritis.

OBJECTIVE: To investigate the ability of hemoglobin (Hgb), a nitric oxide (NO) scavenger, to deplete excess NO and reduce inflammation and injury in synovial tissue from joints with inflammatory arthritis. METHODS: The severity of streptococcal cell wall-induced arthritis was monitored following administration of Hgb. Plasma nitrite and nitrate levels were measured, and inducible NO synthase (iNOS) and cytokine messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMC) and joint tissue were evaluated. RESULTS: Following systemic administration of Hgb to arthritic rats, plasma levels of nitrite and nitrate as well as iNOS mRNA expression in the joints and PBMC were significantly reduced. Moreover, inflammatory cell accumulation and disease pathology in the joint tissue were dramatically attenuated without obvious side effects. Consistent with this reduction in the inflammatory response, cytokine gene expression was decreased in the synovium of Hgb-treated rats. CONCLUSION: Modulation of NO levels through the use of a NO scavenger, Hgb, influences the development and severity of arthritis. These findings suggest that depletion of excess NO by NO scavengers provides a prototype for further exploration of potential treatments for chronic arthritis.